1. Field of the Invention
The present invention relates generally to the fields of ophthalmology, ocular pharmacology and protein chemistry. More specifically, the present invention relates to novel ophthalmologic uses of Protein C.
2. Description of the Related Art
Formation of intraocular fibrin subsequent to ocular surgery, inflammation, hemorrhage or trauma is a serious medical problem. Fibrin deposition can also occur in diabetic eye disease, uveitis and vitreoretinopathy and can severely compromise the outcome of glaucoma filtering or vitreoretinal surgery.
Uveitis is an inflammation of any structure of the uveal tract, which includes the iris, ciliary body or choroid. Anterior uveitis results in a breakdown of the blood-aqueous barrier with concentration of protein in the aqueous that can increase up to a hundred fold compared to the normal state. During inflammation, white blood cells, plasma proteins and inflammatory mediators from blood vessels in the iris and ciliary body are released into the aqueous humor. Activation of the clotting cascade results in fibrin formation in the anterior chamber with detrimental effects on vision.
The possible causes for postoperative fibrinous membrane formation include preexisting vascular incompetance, (e.g., severe diabetes mellitis) uveitis due to surgical trauma, reactions to the intraocular implants and their coating material or infections subsequent to surgery. Regardless, the exact pathogenesis of the postoperative, and other, fibrin responses remains unknown.
The management of severe postoperative fibrin response by current means is often ineffective. Generally, treatment is oriented toward reduction of postoperative inflammation and attempted reestablishment of the blood-ocular barrier using topical or systemically administered corticosteroids. Unfortunately, corticosteroid use is often ineffective and, moreover, can cause complications in patients with diabetes mellitis or glaucoma.
Heparin has been used to reduce fibrin formation but leads to increased bleeding. More recently, attempts have been made to treat ocular fibrin depostion using tissue plasminogen activator. Recombinant human tPA injected intraoccularly has been effective but its use is complicated by increased incidence of intraocular hemorrhage. Moreover, at doses above 25 micrograms, tPA is toxic to the retina. The use of tPA to treat hyphema, a post-traumatic collection of blood in the anterior chamber of the eye, has also been examined with questionable clinical benefits.
The prior art is deficient in the lack of effective means of inhibiting the depostion of fibrin caused by a variety of pathophysiological states. The present invention fulfills this longstanding need and desire in the art.